Corso di Antropologia Molecolare – Lez. 2

L’ANTROPOLOGIA MOLECOLARE OGGI

Gli anni ’90 – Human Genome Project

1984-1987 valutazione fattibilità

1988 nasce HUGO (Human Genome Organization)

obiettivi principali:- sequenziare le 3 milioni di bp che costituiscono il genoma umano- identificare i 20-25 mila geni- salvare le informazioni in database pubblici- sviluppare nuovi strumenti per l’analisi di questi dati- affrontare gli aspetti etici

2003 HGP completato – si da inizio all’era della genomica

2.7$ billion dollars

20 centri di sequenziamento in Cina, Francia, Germania, Inghilterra, Giappone e Stati Uniti – dei 5 più attivi, 4 sono negli Stati Uniti e uno in Inghilterra

Gli anni ’90 – Human Genome Diversity Project

1991-1994 valutazione fattibilità (aspetti statistici, antropologici, molecolari ed etici)

1994-1997 in attesa della valutazione della commissione del NRC (US National Research Council, of the National Academy of Sciences)

fine 1997 consenso ottenuto – attenzione particolare al consenso informato

obiettivo principale: collezione di linee cellulari di linfoblastoidi per la creazione di un set di popolazioni rappresentative della variabilità umana mondiale

perchè? accuratezza e rigenerazionedove? CEPH, Parigiquali popolazioni? da tutto il mondo, campioni donati da genetisti umani

2002 HGDP completato – il set di campioni è conservato al CEPH e disponibile (prima gratuitamente ora con un piccolo contributo) per studi di genetica di popolazione e genetica medica

HGDP-CEPH panel: 1064 individuals in 52 populations

Nel 2000 – HapMap Projectwww.hapmap.org

- catalogue of common genetic variants

- pattern of LD and consequent identification of tagSNPs

- useful for association studies, MA ANCHE for population genomics

objective 1SNPs each 5Kb

result 1SNPs each 1Kb for a total of 3.8 million SNPs

4 populations- 90 European origins from Utah- 45 Han Chinese, Beijing- 45 Japanes, Tokio- 90 Yoruba Nigerian, Ibadan

Rosenberg et al., 2008. Genetic structure of human populations. Science.

test the correspondence of predefined groups with those inferred from individual multilocus genotypes

clustering method that identifies subgroups that have distinctive allele frequencies

CEPH panel; multiplex for 377 STRs

Rosenberg et al., 2008. Genetic structure of human populations. Science.

individuals from the same predefined population nearly always shared similar membership coefficient

world-level boundaries between major clusters mostly correspond to major physical barriers (oceans, Himalaya, Sahara)

Rosenberg et al., 2008. Genetic structure of human populations. Science.

Rosenberg et al., 2008. Genetic structure of human populations. Science.

STRUCTURE

efficiently detects isolated and homogeneous groups

Rosenberg et al., 2008. Genetic structure of human populations. Science.

the amount of among-group variation affects the number of loci required to produce clusters similar to thos obtained with the full data

accuracy decreased considerably whenm only half the sample was used

Rosenberg et al., 2008. Genetic structure of human populations. Science.

main conclusions:

• genetic clusters often corresponded closely to predefined regional or population groups (among exceptions, linguistic similarity did not provide significant grouping criteria)

• consequently, self-reported population ancestry (less intrusive) provides a suitable proxy for genetic ancestry

however,

• wrong structure (defined on self-reported infos) could affect in a significant way the results of association studies

• this is also true for population studies when selection and demographic tests are applied

Li et al., 2008. Worldwide human relationships inferred from genome-wide patterns of variation. Science.

CEPH panel

Illumina Bead Chip 650K (642,690)

N = 938genetic ancestry of each individual

individuals from the same population show similar ancestry proportions –

population structuring robust (confirmed also by PCA)

Li et al., 2008. Worldwide human relationships inferred from genome-wide patterns of variation. Science.

maximum-likelihood tree

sub-saharan africa

middle east

europe

south/central asia

east asia

america

oceania

main result: confirmation of the Out of Africa

consistent with a serial founder effect

scenario in which population expansion involves successive migration of a small fraction of individuals out of the previous location starting from a single origin in sub-Saharan Africa

Li et al., 2008. Worldwide human relationships inferred from genome-wide patterns of variation. Science.

Li et al., 2008. Worldwide human relationships inferred from genome-wide patterns of variation. Science.

small pop sizebottleneck

higher drift

more rapid increase of derived allele frequencies

decrease of ancestral allele frequencies

decrease of the slope

Li et al., 2008. Worldwide human relationships inferred from genome-wide patterns of variation. Science.

Jakobsson et al., 2008. Genotype, haplotype and copy-number variation in worldwide human populations. Nature.

CEPH panel29 populationsN = 485

525,910 SNPs396 CNVs (more than 1kb deletions, insertions, duplications)

Jakobsson et al., 2008. Genotype, haplotype and copy-number variation in worldwide human populations. Nature.

SNPs

CNVs

Jakobsson et al., 2008. Genotype, haplotype and copy-number variation in worldwide human populations. Nature.

SNPs

CNVs

MDS (allele-sharing distance)

Jakobsson et al., 2008. Genotype, haplotype and copy-number variation in worldwide human populations. Nature.

number of variants observed in all five regions

SNPs CNVs

regionally private alleles

81.17%

0-0.91% 2.91-12.33%

61.19%

Jakobsson et al., 2008. Genotype, haplotype and copy-number variation in worldwide human populations. Nature.